Abstract
Potential applications for drugs targeting IL-6 include a range of inflammatory and proliferative disorders, including rheumatoid arthritis, multiple myeloma, post transplant lymphoma, Crohn’s disease and Systemic Lupus. Using the ActivMab® technology, a high-affinity, fully human antagonistic monoclonal antibody (MAb) OP-R003-1 was structurally derived from elsilimomab (B-E8, a murine anti-IL-6 MAb) which had previously been shown to be effective in several proof-of-concept clinical trials. In vitro studies demonstrated that OP-R003-1 shares similar biological properties, including affinity and epitope specificity with its “parent” murine antibody. OP-R003-1 detected human and monkey IL-6 but not murine or rat IL-6. No binding was observed with other IL-6 superfamily members. This novel fully human MAb inhibited the binding of IL-6 to its receptor as evidenced by flow cytometry using U266 cells and also inhibited IL-6 induced cell proliferation in murine B9, human TF1 or U266 cells. The conversion of the murine B-E8 MAb into a fully human MAb will result in an improved therapeutic MAb clinical profile, including reduced immunogenicity and improved half-life, while preserving the specificity and clinical effectiveness of the murine Mab.
Author notes
Disclosure: No relevant conflicts of interest to declare.
